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Objectives: The objective of this study to determine whether body mass index (BMI) in different genders and age groups need different thresholds when predicting chronic non-communicable diseases (CNCDs)., Study Design: This is a cross-sectional study., Methods: Data were obtained from the China Health and Nutrition Survey conducted in 2009. Sequential sample cluster analysis was used to group age according to BMI. Propensity score matching was used to eliminate the influence of age. Receiver operating characteristic curve based on gender and age group was used to evaluate the cut-off values and efficiency of BMI in each group., Results: A total of 8469 individuals were enrolled in this study. Results of sequential sample cluster analyses showed age was divided into three groups: 18-39, 40-59 and 60-99 years. There were significant differences in the distribution of BMI among the three groups for both males and females (P < 0.001). Statistical differences were observed in the distribution of BMI between genders in the 18-39- and 60-99-year-old age groups (P < 0.001). For men, the cut-off values of BMI were ≥25 kg/m 2 , ≥24 kg/m 2 and ≥23 kg/m 2 in the 18-39, 40-59 and 60-99 years old groups, respectively; for women, the corresponding cut-off points were ≥25 kg/m 2 , ≥23 kg/m 2 and ≥25 kg/m 2 in groups., Conclusions: The thresholds for BMI might be different between gender and age group. In addition, it might not be suitable to determine cut-off values of BMI to predict CNCDs for people aged ≥60 years., (Copyright © 2019 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Gut microbes, especially those in the large intestine, are actively involved in nutrient metabolism; however, their impact on host nitrogen (N) metabolism remains largely unknown. This study was designed to investigate the effects of feeding a cocktail of antibiotics (AGM) (ampicillin, gentamycin and metronidazole) on intestinal microbiota, N utilization efficiency, and amino acid (AA) digestibility in cannulated pigs, with the aim of exploring the impact of gut microbiota on host N metabolism. In total, 16 piglets were surgically fitted with a simple distal ileal T-cannula and a jugular venous catheter. The pigs were fed a basal diet without antibiotics (control; CON) or with antibiotics (antibiotic; ANTI), for 2 weeks. The results showed that feeding AGM did not affect weight gain or digestive enzyme activity. The antibiotics increased the concentration of urea N (P&lt;0.05). However, they reduced N utilization, and the total tract apparent digestibility of isoleucine, methionine, valine, tyrosine and total AA (P&lt;0.05). Furthermore, the antibiotics increased the terminal ileum apparent digestibility of CP, phenylalanine, valine, alanine, tyrosine and total AA (P&lt;0.05). AGM markedly altered the composition of the microbiota in the ileum and feces, with a reduction in populations of Bifidobacterium, Lactobacillus and Ruminococcus, and an increase in the abundance of Escherichia coli (P&lt;0.05). The antibiotics also significantly increased the concentration of cadaverine and ammonia, both in ileal digesta and feces (P&lt;0.05), suggesting a marked impact on N metabolism in the intestine. The analyses indicated that the alteration of gut microbiota was correlated with the apparent digestibility of CP and AA in the intestine. These findings suggest that the AGM-induced alteration of gut microbiota may contribute to the change in intestinal N metabolism, and consequently, N excretion from the body. These results also suggest that antibiotics could have a significant effect on host N metabolism. The present study contributes to our understanding of the effects of antibiotics and provides a rational scientific basis for diet formulation during AGM use.

Background and Aims: The American Heart Association has outlined seven cardiovascular health (CVH) metrics, including smoking, body mass index, physical activity, dietary pattern, total cholesterol, and fasting plasma glucose, to define and monitor CVH status. Our study was to evaluate the global CVH in adults., Methods and Results: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and reference lists of relevant articles for studies published between 1 January 2010 and 30 June 2018. Included studies should report the proportions of ideal status for the seven CVH metrics and/or provide the prevalence of overall poor (having 0-2 ideal metrics) or ideal (having 5-7 ideal metrics) CVH status in adults. 88 articles were identified: 75 for the prevalence of ideal CVH metrics, 58 for the proportion of overall poor CVH status, and 55 for the proportion of overall ideal CVH status. Smoking had the highest prevalence of ideal status (69.1%) while dietary pattern has the lowest (12.1%). 32.2% and 19.6% of participants had overall poor and ideal CVH, respectively. Females and young adults had better CVH status when compared to males and older adults. There existed regional variations in ideal CVH metrics and overall CVH status. The overall CVH status had improved over study time., Conclusion: The prevalence of ideal status was low for some metrics, such as dietary pattern, and the overall CVH status was still unsatisfactory. We should continue to measure the CVH status and carry out lifestyle interventions to improve the CVH status in the whole population., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aim: Folate is involved in a number of metabolic pathways. Red blood cell (RBC) folate is a well-established indicator of folate intake. However, studies focused on the association between RBC folate and coronary heart disease (CHD) are limited. The aim of the current study was to investigate the effect of RBC folate concentrations on the presence of CHD in a nationally representative sample of American adults., Methods and Results: In the 1999-2012 National Health and Nutrition Examination Survey (NHANES), 22,499 subjects aged 30-74 years with RBC folate concentrations, CHD status and responses to co-variates questions were included; 822 (3.65%) participants were identified as having CHD. Bio-Rad Quanta Phase II radioassay and microbiological assay were used to measure RBC folate concentrations. Firstly, we treated RBC folate as a categorical variable, based on RBC folate tertiles, and used logistic regression analysis to display the RBC folate and CHD relationship. Secondly, we explored associations using a combination of restricted cubic spline and logistic regression models, stratified by sex. After adjusting for several well-established traditional CHD risk factors, RBC folate was positively related to CHD presence in the total population and the association was more pronounced among males than females. A J-shaped pattern was observed in RBC folate concentrations for females., Conclusion: Elevated RBC folate concentrations were associated with higher CHD risk. Further investigation is needed to test the association in large-scale follow-up studies., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

There is a possibility that the aggresomes that form in the brain in neurodegenerative diseases like Alzheimer's disease (AD) and in the liver where aggresomes like Mallory-Denk Bodies (MDB) form, share mechanisms. MDBs can be prevented by feeding mice sadenosylmethionine (SAMe) or betaine. Possibly these proteins could prevent AD. We compared the literature on MDBs and AD pathogenesis, which include roles played by p62, ubiquitin UBB +1, HSPs70, 90, 104, FAT10, NEDD8, VCP/97, and the protein quality control mechanisms including the 26s proteasome, the IPOD and JUNQ and autophagosome pathways., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Normal placental function is critical to optimize fetal growth and development, but few perinatal studies incorporate placental measures. Our objectives were to link clinical placental pathology records to birth records, and validate an automated abstraction strategy., Methods: Of the 47,329 deliveries at our hospital from 2008 to 2012, we retrieved electronic copies of pathology reports (n = 21,585, 45.4%). Pathology data were extracted with Extensible Markup Language (XML) script using Java and structured query language (SQL) transformed the text information into variables that were linked to delivery data. A subgroup of records was selected for a validation study that compared automated to manual abstraction (n = 144)., Results: Linked birth-placental records included 93% of all preterm (<37 weeks, n = 5108) and 37.1% of term births (n = 14,019). Over 90% of deliveries complicated by preeclampsia, chronic hypertension, or gestational diabetes included pathology data. The validation study indicated excellent agreement, sensitivity and specificity between the two abstraction strategies., Discussion: We demonstrate a reliable approach to electronically integrate placental pathology and delivery data. These linked data provide a platform to identify risk factors and sequelae associated with placental lesions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Few articles have documented regimens and timing of perioperative chemotherapy for bladder cancer in routine practice. Here, we describe practice patterns in the general population of Ontario, Canada., Methods: In this retrospective cohort study, treatment and physician billing records were linked to the Ontario Cancer Registry to describe use of neoadjuvant (NACT) and adjuvant (ACT) chemotherapy among all patients with muscle-invasive bladder cancer treated with cystectomy in Ontario 1994-2008. Time to initiation of ACT (TTAC) was measured from cystectomy. Multivariate Cox regression was used to identify factors associated with overall (OS) and cancer-specific survival (CSS)., Results: Of 2944 patients undergoing cystectomy, 4% (129/2944) and 19% (571/2944) were treated with NACT and ACT, respectively. Five-year OS was 25% [95% confidence interval (CI) 17% to 34%] for NACT, 29% (95% CI 25% to 33%) for ACT cases. Among patients with identifiable drug regimens, cisplatin was used in 82% (253/308) and carboplatin in 14% (43/308). The most common regimens were gemcitabine-cisplatin (54%, 166/308) and methotrexate, vinblastine, doxorubicin, cisplatin (MVAC) (21%, 66/308). Mean TTAC was 10 weeks; 23% of patients had TTAC >12 weeks. TTAC >12 weeks was associated with inferior OS [hazard ratio (HR) 1.28, 95% CI 1.00-1.62] and CSS (HR 1.30, 95% CI 1.00-1.69). In adjusted analyses, OS and CSS were lower among patients treated with carboplatin compared with those treated with cisplatin; OS HR 2.14 (95% CI 1.40-3.29) and CSS HR 2.06 (95% CI 1.26-3.37)., Conclusions: Most patients in the general population receive cisplatin, and this may be associated with superior outcomes to carboplatin. Initiation of ACT beyond 12 weeks is associated with inferior survival. Patients should start ACT as soon as they are medically fit to do so., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The present study aimed to examine the differences in pandemic (H1N1) 2009 vaccination coverage rate between urban and rural areas in China, and to explore factors associated with any urban-rural differences., Study Design: Cross-sectional study., Methods: Data were derived from a cross-sectional telephone survey performed in seven urban and two rural areas soon after the pandemic peak in China, concerning pandemic (H1N1) 2009 vaccination and associated knowledge, attitudes and practices among the general population in China. A total of 10 669 participants aged 18 years and above participated in the study., Results: Vaccination amongst rural residents was less than urban residents (8.9% vs 11.2%, P = 0.002). Among those who have not been immunized, 82.2% of rural respondents showed a willingness to get vaccinated against A/H1N1, significantly higher than that of urban respondents (55.3%). The major barrier to vaccination was reported as 'not being informed to get vaccination', of which there was a greater proportion in rural than urban population (71.9% vs 68.8%, P = 0.009). The analysis revealed a number of factors which contribute to this disparity: previous experience of vaccination against flu, degree of awareness of the free vaccination policy, and sociodemographic differences between urban and rural areas., Conclusions: Significant discrepancies existed in the pandemic (H1N1) 2009 vaccination coverage rate and associated determinants, as well as the intention to get vaccinated between urban and rural residents. To improve the effectiveness of similar vaccination programmes in the future, campaigns for rural people need to be specifically tailored to address disparities in uptake., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

As a novel antibiotic resistance determinant, investigation of the occurrence and characteristics of class 1 integron was performed on nosocomial methicillin-resistant Staphylococcus aureus (MRSA) strains sampled during 2001-2006. Seventy-six out of 179 (42.5%) of the tested strains were found to carry class 1 integrons, with four unique arrays of gene cassettes detected. This is the first report of the comprehensive identification and typing of class 1 integrons in clinical MRSA isolates over a 6-year period, representing the first evidence for class 1 integrons as possible antibiotic resistance determinants in clinical MRSA strains., (© 2010 The Authors. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: To develop and evaluate an applicable model for a community health service (CHS) in an underdeveloped area of China that ensures efficient, convenient and affordable primary healthcare access for all residents., Study Design: The current study was carried out in Puyang, a typical medium-sized city in central-eastern China. Based on the healthcare requirements of the residents in Puyang, a CHS network was set up and its operation was evaluated from 1999 to 2006. The system is characterized by its focus on community health education (CHE)., Methods: Firstly, 8231 residents, selected at random, were surveyed to investigate the healthcare requirements of the local residents. Meanwhile, the operation of the pre-existing healthcare resources was investigated in Puyang. Based on the information gained, a network-based CHS system was proposed and established, with CHE as the major focus. This study compared CHS operation prior to and after establishment of the network. Finally, an analytic hierarchy process based evaluation model was applied to evaluate the operation of the CHS network., Results: There was a high prevalence (86.98 per thousand) of chronic diseases among the residents who participated in this investigation. The majority (84.39%) of the residents who had healthcare requirements resorted to professional health care; the other residents did not have access to health services. Among those residents who sought professional treatment, 71.3% visited primary healthcare institutions. This information reflects the enormous requirement for a CHS in primary health care but the lack of accessibility among the residents; this motivated the authors to establish a system to solve the problem. The improvement in CHS operation after the network was established suggests the importance of a network for optimizing the primary healthcare system. The improvement was indicated by better understanding of the residents regarding the CHS, and enhanced capability of self-monitoring for chronic diseases such as hypertension after the network was established. Moreover, the residents' knowledge of health care was significantly increased and, accordingly, the incidence of health risk behaviour was reduced after the network was established. Furthermore, the CHE index between 1999 and 2006 showed good correlation (r=0.988, p<0.005) with the CHS index, suggesting the important role of CHE in CHS development., Conclusions: A network-characterized CHS system was established in Puyang, and improved the primary healthcare situation. This study provides a feasible model for the development of a CHS in medium and small cities in underdeveloped parts of China., (2010 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Traditional risk factors do not adequately explain coronary heart disease (CHD) risk after kidney transplantation. We used a large, multicenter database to compare traditional and nontraditional CHD risk factors, and to develop risk-prediction equations for kidney transplant patients in standard clinical practice. We retrospectively assessed risk factors for CHD (acute myocardial infarction, coronary artery revascularization or sudden death) in 23,575 adult kidney transplant patients from 14 transplant centers worldwide. The CHD cumulative incidence was 3.1%, 5.2% and 7.6%, at 1, 3 and 5 years posttransplant, respectively. In separate Cox proportional hazards analyses of CHD in the first posttransplant year (predicted at time of transplant), and predicted within 3 years after a clinic visit occurring in posttransplant years 1-5, important risk factors included pretransplant diabetes, new onset posttransplant diabetes, prior pre- and posttransplant cardiovascular disease events, estimated glomerular filtration rate, delayed graft function, acute rejection, age, sex, race and duration of pretransplant end-stage kidney disease. The risk-prediction equations performed well, with the time-dependent c-statistic greater than 0.75. Traditional risk factors (e.g. hypertension, dyslipidemia and cigarette smoking) added little additional predictive value. Thus, transplant-related risk factors, particularly those linked to graft function, explain much of the variation in CHD after kidney transplantation.

Background: Thrombotic thrombocytopenic purpura (TTP) is associated with congenital and acquired deficiency of ADAMTS-13, a metalloprotease that cleaves von Willebrand factor (VWF) and reduces its adhesive activity. Mutations throughout the ADAMTS13 gene have been identified in congenital TTP patients, most of whom have initial episodes during infancy or in early childhood., Patients and Methods: We report the case of an adult male who was diagnosed with idiopathic thrombocytopenic purpura at age 34, and with TTP 14 years later. The patient was compound heterozygous for an 18 bp in-frame deletion (C365del) in the disintegrin domain and a point mutation of R1060W in the seventh thrombospondin domain of the ADAMTS-13 gene., Conclusions: In vitro studies found that C365del and R1060W severely impair ADAMTS-13 synthesis in transfected Hela cells, whereas the deletion mutant also failed to cleave VWF under static and flow conditions.

Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance.

Adiponectin is a cytokine secreted specifically by adipocytes that has been proposed to enhance insulin sensitivity and prevent atherosclerosis. Adiponectin receptors (adipoR1 and adipoR2) are recently found in mice which act as receptors for globular and full-length adiponectin to mediate the fatty-acid oxidation and glucose uptake in muscle and liver. The primary goal of this study was to examine chromosome localization of porcine adiponectin and adiponectin receptors and the gene expression pattern in various tissues of pigs of the three genes. Radiation hybrid mapping demonstrated that porcine adiponectin, adipoR1 and adipoR2 were located to chromosome13q36-41, 10p11 and 5q25, in the regions that were syntenic to the homologs of human genes, respectively. Semi-quantitative RT-PCR showed that porcine adiponectin mRNA was specifically expressed in adipose tissue and porcine adipoR1 and adipoR2 mRNA were ubiquitously expressed in many tissues except brain. Comparison to adipoR2 mRNA which was highly expressed in liver, heart, kidney, adipose tissues and lung, adipoR1 mRNA was expressed at relatively high levels in porcine muscle, leukocytes and epididymis. Our data provide basic molecular information useful for the further investigation on the function of the three genes.

Previously we have shown that blocking bone morphogenetic protein (BMP) receptor signaling by a dominant negative BMP receptor causes neurogenesis in Xenopus animal caps (ACs), whereas the physiological neural inducer noggin acts as a homodimer physically binding to BMP-4 and disrupting its signaling at the ligand level. The present study attempted to elucidate the relationship between the structure and function of noggin. By replacing some cysteine residues with serine residues through a site-directed mutagenesis strategy, we generated three noggin mutants, C145S, C205S, and C(218, 220, 222)S (3CS). Although mRNAs encoded by these mutants were translated as efficiently as wild-type (WT) noggin mRNA, they behaved differently when expressed in vivo. Expression of WT noggin or C205S in Xenopus ACs converted the explants (prospective ectoderm) into neural tissue, indicated by the neural-like morphology and expression of the pan neural marker NCAM in the ACs. In contrast, ACs expressing C145S or 3CS sustained an epidermal fate like the control caps. Similar results were observed in the mesoderm where C205S (but not C145S and 3CS) displayed dorsalizing activity as well as WT noggin. Altogether, our results suggest that Cys145 alone or Cys(218, 220, 222) as a whole in noggin protein is required for the biological activities of noggin, probably participating in the dimerization of noggin with BMP-4 or itself., (Copyright 2000 Academic Press.)

In adult vertebrates, fibroblast growth factor (FGF) synergizes with many hematopoietic cytokines to stimulate the proliferation of hematopoietic progenitors. In vertebrate development, the FGF signaling pathway is important in the formation of some derivatives of ventroposterior mesoderm. However, the function of FGF in the specification of the embryonic erythropoietic lineage has remained unclear. Here we address the role of FGF in the specification of the erythropoietic lineage in the Xenopus embryo. We report that ventral injection of embryonic FGF (eFGF) mRNA at as little as 10 pg at the four-cell stage suppresses ventral blood island (VBI) formation, whereas expression of the dominant negative form of the FGF receptor in the lateral mesoderm, where physiologically no blood tissue is formed, results in a dramatic expansion of the VBI. Similar results were observed in isolated ventral marginal zones and animal caps. Bone morphogenetic protein-4 (BMP-4) is known to induce erythropoiesis in the Xenopus embryo. Therefore, we examined how the BMP-4 and FGF signaling pathways might interact in the decision of ventral mesoderm to form blood. We observed that eFGF inhibits BMP-4-induced erythropoiesis by differentially regulating expression of the BMP-4 downstream effectors GATA-2 and PV.1. GATA-2, which stimulates erythropoiesis, is suppressed by FGF. PV.1, which we demonstrate to inhibit blood development, is enhanced by FGF. Additionally, PV.1 and GATA-2 negatively regulate transcription of each other. Thus, BMP-4 induces two transcription factors which have opposing effects on blood development. The FGF and BMP-4 signaling pathways interact to regulate the specification of the erythropoietic lineage., (Copyright 1999 Academic Press.)

A novel chemiluminescence (CL) system for ammonium ion combined with flow-injection analysis is presented in this paper. It is based on the CL reaction between luminol, immobilized electrostatically on an anion-exchange column, and chlorine electrochemically generated on-line via a platinum electrode from hydrochloric acid in a coulometric cell. Ammonium ion reacts with chlorine and decreases the observed CL intensity. The system responds linearly to ammonium ion concentration in the range 1.0-100 muM, and the detection limit is 0.4 muM. A complete analysis, including sampling and washing, could be performed in 1 min with a relative standard deviation of <6.0%. The system is stable for over 500 determinations and has been applied successfully to the determination of ammonium ion in rainwater samples.

The hepatic biotransformation in the rat and hamster of 23(R)-hydroxychenodeoxycholic acid (23(R)OH-CDCA), the alpha-hydroxy derivative of CDCA, was defined; some physiological and physicochemical properties were also assessed. 23(R)OH-CDCA was isolated from duck bile; [24-14C]23(R)OH-CDCA was synthesized. The compound was administered intravenously to anesthetized biliary fistula rats at doses of 1, 3, or 5 mu mol/kg-min and to hamsters at 3 mu mol/min-kg. Biliary bile acids and radioactivity were analyzed by thin-layer chromatography (TLC), high pressure liquid chromatography (HPLC), and gas chromatography-mass spectrometry (GC-MS). Recovery of radioactivity in bile was incomplete (50-70% of infused dose); some was also recovered as breath 14CO2. Radioactivity in bile was present as unchanged compound (25-50%, dose-dependent) and its conjugates (with taurine, with glycine, or with glucuronate). Nor-CDCA (C23) was present in bile (in both unconjugated and conjugated form), indicating that 23(R)OH-CDCA had undergone oxidative decarboxylation (alpha-oxidation) with loss of the C-24 carboxyl group. The alpha-oxidation was 20 +/- 5% (mean +/- SD) of administered dose in the rat and was not dose-dependent; in hamsters, alpha-oxidation was 35 +/- 8%. In rats, the S isomer of 23OH-CDCA also underwent alpha-oxidation (10 +/- 2%). Nor-CDCA also underwent 6beta-hydroxylation to form nor-alpha-muricholic acid, as well as reduction of its C-23 carboxyl group to form the C23 alcohol. The taurine conjugate of 23(R)OH-CDCA [23(R)OH-CDC-tau] was prepared synthetically and characterized by 1H-NMR. By surface tension measurements, it had a critical micellization concentration (CMC) of 3.5 mM (in 0.15 M Na+), as compared to 1.8 mM for CDC-taurine. Aqueous solubility of 23(R)OH-CDCA increased markedly above pH 5, compared to pH 7 for CDCA. When incubated with cholylglycine hydrolase, 23(R)OH-CDC-tau was deconjugated at a rate one-fourth that of CDC-tau. It is concluded that the presence of a 23(R)-hydroxyl group in a 3alpha, 7alpha-dihydroxy bile acid alters its metabolism in the rodent hepatocyte, as evidenced by inefficient conjugation with taurine or glycine, alpha-oxidation to nor (C23) bile acid, and reduction of the nor bile acid to the primary alcohol. The taurine conjugate of 23(R)OH-CDCA, a major biliary bile acid of marine mammals and wading birds, is a biological detergent with properties superior to those of the taurine conjugate of CDCA. Natural C23 nor-bile acids may be formed by alpha-oxidation of alpha-hydroxy C24 bile acids.

A modified computer program SCTPT for the computation of formation constants of extraction complexes with two-phase pH titration data by using the Marquardt-Fletcher algorithm is described. It can be used to deal with extraction systems which consist of a metal, an acidic extractant and a neutral synergistic reagent with no need of new subroutine. It has been applied successfully to the Pb-PMBP(1-phenyl-3-methyl-4-benzoyl-pyrazolone-5)-TBP (tributyl phosphate) system. The results obtained are in agreement with those published in the literature.

Synergistic and antagonistic effects on genotoxicity of mixtures of four chemicals; i.e., lead tetraacetate (LTA), arsenic trioxide (ATO), dieldrin (DED), and tetrachloroethylene (TCE), were evaluated by the Tradescantia-micronucleus (Trad-MCN) assay. The chemicals were mixed in ratios of 1:1, 1:2 and 2:1 for mixtures of two chemicals and 1:1:1 each for three chemicals. The concentration of stock solution of these chemicals was around the minimum effective dose (MED) or below the MED for these chemicals as reported by Sandhu et al. (1989). Treatments were applied to plant cuttings by hydroponic uptake of the mixed solutions through the stems of the plant for 30 h followed by fixation of the flower buds in aceto-alcohol (1:3 ratio) without a recovery period. Microslides were prepared for scoring MCN frequencies. Results of two series of repeated experiments indicated that all mixtures of LTA/ATO exhibited antagonistic effects. On the other hand, all mixtures of TCE and DED exhibited synergistic effect. These data indicate that for evaluating biological hazards at chemical waste sites, it is prudent to evaluate the genotoxicity of complex chemical mixtures as these exist in nature because the biological effects based on evaluating individual chemicals may not be true predictors of the interactive effects of the pollutants.

Digoxin-Like Immunoreactive Factors (DLIF) which cross-react with antidigoxin antibodies are present in elevated concentrations in patients on hemodialysis, uremia, hypertensives, liver failure, pre-eclampsia and premature birth. DLIF may have a potential role as a natriuretic hormone with a speculated low molecular weight (less than 1000). We studied the dialyzability and bindings of DLIF with serum components in hemodialysis patients. We analyzed DLIF concentrations in sera and protein free ultrafiltrates of 31 patients and 22 normal volunteers using a fluorescence polarization assay for digoxin. The DLIF concentrations were expressed as nmol/L Digoxin Equivalent. The gel filtration analysis was done using three different Bio-Gel columns with molecular weight cut-offs of 10,000, 20,000 and 40,000. Molecules with lower molecular weight than cut-off were absorbed in the column. Only 3 out of 22 normal volunteers (13.6%) showed measurable DLIF. However 23 out of 31 patients (74.2%) showed measurable DLIF. The concentrations of DLIF were significantly higher in patients with renal failure on hemodialysis (P less than 0.05) by both chi-squared and Fisher's exact test. We observed no statistically significant difference in the concentrations of DLIF in pre and post-dialysis sera, indicating that DLIF were not filtered during hemodialysis. We observed no DLIF activity in the protein free ultrafiltrates of any DLIF positive sera (patients and normal volunteers), indicating that unlike digoxin (where we observed 70-80% of total digoxin concentrations in ultrafiltrates), DLIF were strongly bound to serum components. With Bio-Gel filtration experiments (five different serum pools), we recovered all DLIF activities in the fraction equivalent to the void volume of the column with Bio-Gel P6 and P10 columns, indicating that DLIF were almost completely bound to serum components with molecular weight greater than 20,000. On the other hand, we recovered no DLIF activities in the void volume when the same serum pools were passed through the Bio-Gel P30 column, indicating that DLIF were strongly bound to serum macromolecules with molecular weight less than 40,000. In sharp contrast, when serum containing digoxin was subjected to the same series of experiments, we recovered only 20-30% of digoxin concentrations in void volume with all three columns as expected since digoxin is only 25% bound to albumin (MW 67,000).

7 chemicals commonly found at the industrial waste sites were tested with the Tradescantia-Micronucleus (Trad-MCN) assay to evaluate their clastogenic potential. Chemicals selected from the US EPA Superfund Priority 1 list were: aldrin, arsenic trioxide, 1,2-benz[a, h]anthracene, dieldrin, heptachlor, lead tetraacetate and tetrachloroethylene. Results of repeated tests for clastogenicity yielded the minimum effective dose (MED) for clastogenicity of 0.44 ppm for lead tetraacetate, 1.88 ppm for heptaclor, 3.81 ppm for dieldrin and arsenic trioxide and 1,2-benz[a, h]anthracene yielded positive responses at the MED of 3.96 ppm and 12.50 ppm respectively. Aldrin and tetrachloroethylene were considered to be immiscible with water, and the tests yielded negative responses. Tetrachloroethylene in gaseous state was also used to treat the flower buds. Results of tetrachloroethylene vapor phase treatment yielded a positive response at the MED of 30 ppm/min after a 2-h exposure. 5 chemicals determined to be clastogens by this test were ranked according to their MED in the descending order of potency as follows: lead tetraacetate, heptachlor, dieldrin, arsenic trioxide and 1,2-benz[a, h]anthracene. Results of this study indicate that the Trad-MCN bioassay could be effectively utilized for assessing the potential clastogenicity of the chemicals commonly found at the industrial hazardous waste sites.

Effects of histidine or methionine imbalance and dietary levels (3-50%) of casein on food intake and preference of young, adult, and diabetic (2.5 month old) rats were examined. Depressions in food intake and growth caused by ingestion of the imbalanced diet were greatest in young rats and least or absent in diabetic rats. Alloxan diabetes induced hyperphagia and elevated concentrations of plasma branched-chain amino acids and decreased concentrations of tryptophan and tyrosine. The diabetic rats fed the imbalanced diet for 9 days had a higher concentration of the limiting amino acid in the plasma than the adult normal rats fed the same diet. The diabetic rats preferred the imbalanced diet over a protein-free diet when they were fed these diets concurrently. Ingestion of the imbalanced diet by normal rats caused greater changes in plasma and brain amino acid patterns than did the protein-free diet. Unlike the diabetic rats, the normal rats, especially the young rats, strongly preferred the protein-free diet over the imbalanced diet. The normal rats also preferred a 10% casein diet supplemented with L-methionine over a low or high casein diet. It seemed that young rats were able to select a protein diet that supported maximal growth when proportions of dietary amino acids were balanced. It also seemed that the susceptibility of the rats to amino acid imbalance varied directly with the status of overall protein synthesis of the animals.